Abstract Our recent investigations show higher kidney cancer (CaK) mortality and higher smoking rates in rural populations, including rural Illinois. We posit that rural patients in Southern and Central Illinois will have lower health literacy (HL) and less knowledge about the relationship between smoking and CaK than urban patients, regardless of socioeconomic status. We also posit that despite high levels of symptoms, rural patients will report lower levels of disease impact and bother. Thus, we expect to find correlations of different magnitudes between symptom levels and bother in rural compared to urban patients. We propose the following specific aims: i. Examine whether health literacy and cancer literacy differ by geographic region (rural vs. urban). ii. Investigate whether knowledge of smoking and kidney cancer differs by geographic region. iii. Compare threshold for the bothersomeness of urologic symptoms by geographic region. To address these aims, we will examine health and cancer message literacy, smoking and CaK knowledge, and threshold of bothersomeness among 300 patients recruited from rural and urban serving primary care and urology clinics. We will examine if rural participants have lower health and cancer message literacy, less CaK-specific knowledge, and higher thresholds for disease bother compared with urban participants, controlling for smoking history, personal and family history of cancer, and socio-demographics. This proposal addresses an important health concern as CaK is the fifth most common malignancy in the US, and rates for new CaK cases have been rising over the last decade. Rural populations in Illinois are at an increased risk and their HL and knowledge about smoking/ CaK is unknown. Examining HL, CaK risk factor knowledge, and thresholds for bothersomeness in rural populations is novel and significant. It is the first step in creating innovative ways to improve smoking cessation and prevent CaK in this high-risk population. These pilot results will strengthen our potential for future external funding as they will indicate whether HL, cancer message literacy, CaK knowledge and/or threshold for bothersomeness differ by rural vs. urban residence. We will use these results as the basis for an R01 grant application to develop and test an intervention to increase knowledge about the association between smoking and CaK among rural populations. In a second R01, we plan to examine other factors (i.e., interpersonal-, organizational- and community-level factors) affecting CaK incidence and mortality in multi-level analyses. The pilot findings generated by this proposed study will therefore be critical in multiple future grant applications from this new collaborative group of investigators. An innovative aspect of this proposal is the measurement of differences in the level of urologic symptoms required before they become bothersome enough to seek help. This proposal has regional and national implications: HL and knowledge differences between urban and rural populations will point the way to targeted smoking cessation programs for rural residents, has implications for urology density and workforce distribution as well opening the door for renal cancer genomics and biomarkers.